Mammoth interatrial septal aneurysm in the ICE age

<p>Abstract</p> <p>Background</p> <p>Intracardiac echocardiography (ICE) is a useful imaging modality that is now being used more widely to assist in the percutaneous closure of atrial septal defects (ASD) and patent foramen ovales (PFO).</p> <p>Case presentation</p> <p>A 42 year old lady with a history of transient ischaemic attacks and migraine underwent percutaneous closure of an ASD. Intraprocedural ICE demonstrated a mammoth billowing multiperforated interatrial septal aneurysm in association with a secondum ASD.</p> <p>Conclusion</p> <p>ICE provides excellent adjuvant imaging during percutaneous closure of intracardiac shunts, in this case demonstrating a 'mammoth' interatrial septal aneurysm.</p

The effect of immunomodulatory drugs on aortic stenosis: a Mendelian randomisation analysis

There are currently no approved pharmacological treatment options for aortic stenosis (AS), and there are limited identified drug targets for this chronic condition. It remains unclear whether inflammation plays a role in AS pathogenesis and whether immunomodulation could become a therapeutic target. We evaluated the potentially causal association between inflammation and AS by investigating the genetically proxied effects of tocilizumab (IL6 receptor, IL6R, inhibitor), canakinumab (IL1β inhibitor) and colchicine (β-tubulin inhibitor) through a Mendelian randomisation (MR) approach. Genetic proxies for these drugs were identified as single nucleotide polymorphisms (SNPs) in the gene, enhancer or promoter regions of IL6R, IL1β or β-tubulin gene isoforms, respectively, that were significantly associated with serum C-reactive protein (CRP) in a large European genome-wide association study (GWAS; 575,531 participants). These were paired with summary statistics from a large GWAS of AS in European patients (653,867 participants) to then perform primary inverse-variance weighted random effect and sensitivity MR analyses for each exposure. This analysis showed that genetically proxied tocilizumab was associated with reduced risk of AS (OR 0.56, 95% CI 0.45–0.70 per unit decrease in genetically predicted log-transformed CRP). Genetically proxied canakinumab was not associated with risk of AS (OR 0.80, 95% CI 0.51–1.26), and only one suitable SNP was identified to proxy the effect of colchicine (OR 34.37, 95% CI 1.99–592.89). The finding that genetically proxied tocilizumab was associated with reduced risk of AS is concordant with an inflammatory hypothesis of AS pathogenesis. Inhibition of IL6R may be a promising therapeutic target for AS management

The effect of immunomodulatory drugs on aortic stenosis: a Mendelian randomisation analysis

There are currently no approved pharmacological treatment options for aortic stenosis (AS), and there are limited identified drug targets for this chronic condition. It remains unclear whether inflammation plays a role in AS pathogenesis and whether immunomodulation could become a therapeutic target. We evaluated the potentially causal association between inflammation and AS by investigating the genetically proxied effects of tocilizumab (IL6 receptor, IL6R, inhibitor), canakinumab (IL1β inhibitor) and colchicine (β-tubulin inhibitor) through a Mendelian randomisation (MR) approach. Genetic proxies for these drugs were identified as single nucleotide polymorphisms (SNPs) in the gene, enhancer or promoter regions of IL6R, IL1β or β-tubulin gene isoforms, respectively, that were significantly associated with serum C-reactive protein (CRP) in a large European genome-wide association study (GWAS; 575,531 participants). These were paired with summary statistics from a large GWAS of AS in European patients (653,867 participants) to then perform primary inverse-variance weighted random effect and sensitivity MR analyses for each exposure. This analysis showed that genetically proxied tocilizumab was associated with reduced risk of AS (OR 0.56, 95% CI 0.45–0.70 per unit decrease in genetically predicted log-transformed CRP). Genetically proxied canakinumab was not associated with risk of AS (OR 0.80, 95% CI 0.51–1.26), and only one suitable SNP was identified to proxy the effect of colchicine (OR 34.37, 95% CI 1.99–592.89). The finding that genetically proxied tocilizumab was associated with reduced risk of AS is concordant with an inflammatory hypothesis of AS pathogenesis. Inhibition of IL6R may be a promising therapeutic target for AS management

Association between pre-existing cardiovascular disease, mortality and cardiovascular outcomes in hospitalised patients with COVID-19

BackgroundPre-existing cardiovascular disease and cardiovascular risk factors are common in patients with COVID-19 and there remain concerns for poorer in-hospital outcomes in this cohort. We aimed to analyse the relationship between pre-existing cardiovascular disease, mortality and cardiovascular outcomes in patients hospitalised with COVID-19 in a prospective, multicentre observational study.MethodThis prospective, multicentre observational study included consecutive patients of age ≥18 in their index hospitalisation with laboratory-proven COVID-19 in Australia. Patients with suspected but not laboratory-proven COVID-19 and patients with no available past medical history were excluded. The primary exposure was pre-existing cardiovascular disease, defined as a composite of coronary artery disease, heart failure or cardiomyopathy, atrial fibrillation or flutter, severe valvular disease, peripheral arterial disease and stroke or transient ischaemic attack. The primary outcome was in-hospital mortality. Secondary outcomes were clinical cardiovascular complications (new onset atrial fibrillation or flutter, high-grade atrioventricular block, sustained ventricular tachycardia, new heart failure or cardiomyopathy, pericarditis, myocarditis or myopericarditis, pulmonary embolism and cardiac arrest) and myocardial injury.Results1,567 patients (mean age 60.7 (±20.5) years and 837 (53.4%) male) were included. Overall, 398 (25.4%) patients had pre-existing cardiovascular disease, 176 patients (11.2%) died, 75 (5.7%) had clinical cardiovascular complications and 345 (37.8%) had myocardial injury. Patients with pre-existing cardiovascular disease had significantly increased in-hospital mortality (aOR: 1.76 95% CI: 1.21–2.55, p = 0.003) and myocardial injury (aOR: 3.27, 95% CI: 2.23–4.79, p &lt; 0.001). There was no significant association between pre-existing cardiovascular disease and in-hospital clinical cardiovascular complications (aOR: 1.10, 95% CI: 0.58–2.09, p = 0.766). On mediation analysis, the indirect effect and Sobel test were significant (p &lt; 0.001), indicating that the relationship between pre-existing cardiovascular disease and in-hospital mortality was partially mediated by myocardial injury. Apart from age, other cardiovascular risk factors such as diabetes, hypercholesterolemia and hypertension had no significant impact on mortality, clinical cardiovascular complications or myocardial injury.ConclusionsPre-existing cardiovascular disease is associated with significantly higher mortality in patients hospitalised with COVID-19. This relationship may be partly explained by increased risk of myocardial injury among patients with pre-existing cardiovascular disease which in turn is a marker associated with higher mortality

The validity and reliability of consumer-grade activity trackers in older, community-dwelling adults: a systematic review

Objective: To understand the validity and reliability of consumer-grade activity trackers (consumer wearables) in older, community-dwelling adults.Methods: A systematic review of studies involving adults aged over 65 years who underwent physical activity monitoring with consumer wearables. A total of 7 observational studies qualified, identified from electronic databases: MEDLINE, EMBASE, Cochrane Library and others (2014 to 2018). Validity was interpreted using correlation coefficients (CC) and percentage error for agreement between reference devices or gold-standard validation methods. Reliability was compared using mean differences or ranges (under- or overestimation) of step count and activity time.Results: Total sample size was 290 adults, mean age of 70.2±4.8 years and females constituting 46.7±26.1%. The studies evaluated eight different consumer wearables used by community-dwelling adults with a range of co-morbidities. Daily step count for all consumer wearables correlated highly with validation criterion, especially the ActiGraph device: intraclass correlation coefficients (ICC) were 0.94 for Fitbit One, 0.94 for Zip, 0.86 for Charge HR and 0.96 for Misfit Shine. Slower walking pace and impaired ambulation reduced the levels of agreement. Daily step count captured by Fitbit Zip was on average 7117 (±5,880.6), which was overestimated by five of the eight consumer wearables compared with reference devices (range 167.6 to 2,690.3 steps/day). Measurement of activity duration was accurate compared with reference devices, yet less so than step count.Conclusion: In older, community-dwelling adults, consumer wearables accurately measure step count and activity duration, as confirmed by reference devices and validation methods. Further research is required to understand how co-morbidities, gait and activity levels interact with monitoring in free-living environments

Current Concepts on Antiplatelet Therapy: Focus on the Novel Thienopyridine and Non-Thienopyridine Agents

Thienopyridines are a class of drug targeting the platelet adenosine diphosphate (ADP) 2 receptor. They significantly reduce platelet activity and are therefore clinically beneficial in settings where platelet activation is a key pathophysiological feature, particularly myocardial infarction. Ticlopidine, the first of the class introduced to clinical practice, was soon challenged and almost completely replaced by clopidogrel for its better tolerability. More recently, prasugrel and ticagrelor have been shown to provide a more powerful antiplatelet action compared to clopidogrel but at a cost of higher risk of bleeding complications. Cangrelor, a molecule very similar to ticagrelor, is currently being evaluated against clopidogrel. Considering the key balance of ischemic protection and bleeding risk, this paper discusses the background to the development of prasugrel, ticagrelor, and cangrelor and aims to characterise their risk-benefit profile and possible implementation in daily practice